De-mystifying the ‘Mixifusor’

Total intravenous anesthesia (TIVA) using a mixture of propofol and remifentanil in the same syringe has become an accepted technique in Pediatric Anesthesia. A survey by a group of respected UK anesthetists demonstrated a low incidence of serious complications, related to the pharmacology and dose of the drugs. However, a current guideline for the safe use of TIVA recommends against this practice. Pharmaceutical concerns include the physical stability of the emulsion when remifentanil is mixed with propofol; changes in drug concentration over time; nonuniform mixing of propofol and remifentanil; the risk of bacterial contamination; and the potential for drug administration errors. Propofol and remifentanil have markedly different pharmacokinetic profiles. When remifentanil is mixed with propofol and delivered as a target-controlled infusion (TCI) of propofol, remifentanil delivery is not target-controlled but passively follows the variable infusion rates calculated by the syringe driver to deliver predicted plasma or effect-site concentrations of propofol. The pharmacokinetic consequences can be illustrated using pharmacokinetic modeling similar to that used in TCI pumps. The clinical consequences reflect the dose-dependent pharmacodynamics of remifentanil. Increasing the target propofol concentration produces a rapid increase and peak in remifentanil concentration that risks apnea, bradycardia, and hypotension, especially with higher concentrations of remifentanil. The faster decline in remifentanil concentration with falling propofol concentrations risks inadequate narcosis and unwanted responses to surgical stimuli. Remifentanil delivery is inflexible and dosing cannot be adjusted to the clinical need and responses of individual patients. The medicolegal considerations are stark. In UK and EU Law, mixing propofol and remifentanil creates a new, unlicensed drug and the person mixing takes on the responsibilities of manufacturer. If a patient receiving anesthesia in the form of a mixed propofol-remifentanil infusion suffered a critical incident or actual harm, the clinician's practice may come under scrutiny and criticism, potentially involving a legal challenge and the Medical Regulator

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size). Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers:Study protocol

Abstract Background Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. Method/design Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level – i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April–September) using body-mounted UV sensors. Discussion This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. Trial registration ISRCTN15888934 retrospectively registered 15.01.2018

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Defects, Dopants and Lithium Mobility in Li ₉ v ₃ (P ₂ O ₇ ) ₃ (PO ₄ ) ₂

Layered Li9V3(P2O7)3(PO4)2 has attracted considerable interest as a novel cathode material for potential use in rechargeable lithium batteries. The defect chemistry, doping behavior and lithium diffusion paths in Li9V3(P2O7)3(PO4)2 are investigated using atomistic scale simulations. Here we show that the activation energy for Li migration via the vacancy mechanism is 0.72 eV along the c-axis. Additionally, the most favourable intrinsic defect type is Li Frenkel (0.44 eV/defect) ensuring the formation of Li vacancies that are required for Li diffusion via the vacancy mechanism. The only other intrinsic defect mechanism that is close in energy is the formation of anti-site defect, in which Li and V ions exchange their positions (1.02 eV/defect) and this can play a role at higher temperatures. Considering the solution of tetravalent dopants it is calculated that they require considerable solution energies, however, the solution of GeO2 will reduce the activation energy of migration to 0.66 eV

Lithium diffusion in Li₅FeO₄

The anti-fluorite type Li5FeO4 has attracted significant interest as a potential cathode material for Li ion batteries due to its high Li content and electrochemical performance. Atomic scale simulation techniques have been employed to study the defects and Li ion migration in Li5FeO4. The calculations suggest that the most favorable intrinsic defect type is calculated to be the cation anti-site defect, in which Li+ and Fe3+ ions exchange positions. Li Frenkel is also found to be lower in this material (0.85 eV/defect). Long range lithium diffusion paths were constructed in Li5FeO4 and it is confirmed that the lower migration paths are three dimensional with the lowest activation energy of migration at 0.45 eV. Here we show that doping by Si on the Fe site is energetically favourable and an efficient way to introduce a high concentration of lithium vacancies. The introduction of Si increases the migration energy barrier of Li in the vicinity of the dopant to 0.59 eV. Nevertheless, the introduction of Si is positive for the diffusivity as the migration energy barrier increase is lower less than that of the lithium Frenkel process, therefore the activation energy of Li diffusion

Defects, Dopants and Sodium Mobility in Na₂MnSiO₄

Sodium manganese orthosilicate, Na2MnSiO4, is a promising positive electrode material in rechargeable sodium ion batteries. Atomistic scale simulations are used to study the defects, doping behaviour and sodium migration paths in Na2MnSiO4. The most favourable intrinsic defect type is the cation anti-site (0.44 eV/defect), in which, Na and Mn exchange their positions. The second most favourable defect energy process is found to be the Na Frenkel (1.60 eV/defect) indicating that Na diffusion is assisted by the formation of Na vacancies via the vacancy mechanism. Long range sodium paths via vacancy mechanism were constructed and it is confirmed that the lowest activation energy (0.81 eV) migration path is three dimensional with zig-zag pattern. Subvalent doping by Al on the Si site is energetically favourable suggesting that this defect engineering stratergy to increase the Na content in Na2MnSiO4 warrants experimental verification

The cancer patient and cardiology

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.</p

The effects of patient characteristics on ADHD diagnosis and treatment: a factorial study of family physicians

<p>Abstract</p> <p>Background</p> <p>Attention Deficit Hyperactivity Disorder (ADHD) is a costly and prevalent disorder in the U.S., especially among youth. However, significant disparities in diagnosis and treatment appear to be predicted by the race and insurance status of patients.</p> <p>Methods</p> <p>This study employed a web-based factorial survey with four ADHD cases derived from an ADHD clinic, two diagnosed with ADHD in actual evaluation, and two not. Randomized measures included race and insurance status of the patients. Participants N = (187) included clinician members of regional and national practice-based research networks and the U.S. clinical membership of the Society of Teachers of Family Medicine. The main outcomes were decisions to 1) diagnose and 2) treat the cases, based upon the information presented, analyzed via binary logistic regression of the randomized factors and case indicators on diagnosis and treatment.</p> <p>Results</p> <p>ADHD-positive cases were 8 times more likely to be diagnosed and 12 times more likely to be treated, and the male ADHD positive case was more likely to be diagnosed and treated than the female ADHD positive case. Uninsured cases were significantly more likely to be treated overall, but male cases that were uninsured were about half as likely to be diagnosed and treated with ADHD. Additionally, African-American race appears to increase the likelihood of medicinal treatment for ADHD and being both African-American and uninsured appears to cut the odds of medicinal treatment in half, but not significantly.</p> <p>Conclusions</p> <p>Family physicians were competent at discerning between near-threshold ADHD-negative and ADHD positive cases. However, insurance status and race, as well as gender, appear to affect the likelihood of diagnosis and treatment for ADHD in Family Medicine settings.</p